2. Academic Validation
  3. m6A modification of lipoyltransferase 1 inhibits bladder cancer progression by activating cuproptosis

m6A modification of lipoyltransferase 1 inhibits bladder cancer progression by activating cuproptosis

  • Oncogene. 2024 Sep;43(40):2971-2985. doi: 10.1038/s41388-024-03139-5.
Kaixuan Du # 1 2 3,  Yongbo Luo # 1 2 3,  Lei Zhang # 4,  Youmiao Zeng 1 2 3,  Yiheng Dai 1 2 3,  Mengda Ren 1 2 3,  Wenbang Pan 1 2 3,  Yuanhao Liu 1 2 3,  Fengyan Tian 5,  Lijie Zhou 6 7 8,  Chaohui Gu 9 10 11
Affiliations

Affiliations

  • 1 Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • 2 Department of Urology, Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • 3 Unit of Day Surgery Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • 4 Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
  • 5 Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. 82600086@qq.com.
  • 6 Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. zhouxiaozhou29@126.com.
  • 7 Department of Urology, Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. zhouxiaozhou29@126.com.
  • 8 Unit of Day Surgery Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. zhouxiaozhou29@126.com.
  • 9 Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. zgwhgch@hotmail.com.
  • 10 Department of Urology, Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. zgwhgch@hotmail.com.
  • 11 Unit of Day Surgery Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. zgwhgch@hotmail.com.
  • # Contributed equally.
PMID: 39198615 DOI: 10.1038/s41388-024-03139-5
Abstract

Cuproptosis, a cell death process caused by copper ions, is mediated by protein lipidation related to lipoic acid metabolism. There is a close connection between Cuproptosis and the progression and prognosis of various tumors. Here, we identified lipoyltransferase 1 (LIPT1), a key gene related to Cuproptosis, was downregulated in bladder Cancer (BLCA) and was associated with unfavorable patient prognosis. Restoring the LIPT1 expression in BLCA cells suppressed the proliferation and promoted Cuproptosis. Moreover, the consequences of RNA Sequencing and Bodipy staining showed that the metabolic pathway mediated by LIPT1 inhibited the accumulation of lipid droplets in cells, disrupted endoplasmic reticulum (ER) homeostasis, and promoted cell Apoptosis. Additionally, overexpression of LIPT1 not only repressed the proliferation rate of BLCA cells in vitro but also in vivo. Mechanistically, YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) promoted the degradation of LIPT1 mRNA in a m6A-dependent manner. In summary, these conclusions reveal that LIPT1 promotes cuprotosis and ER stress to inhibit the progression of BLCA, indicating that LIPT1 will provide a powerful treatment direction and drug target for treating BLCA.

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